Advanced Lipid Testing

February 2nd, 2024

For decades, the debate about the causes of heart disease has revolved around cholesterol, particularly “good” versus “bad” cholesterol. But despite the widespread use of statins and the successful reduction of LDL-C (the “bad” cholesterol), heart disease continues to be the leading cause of death in the United States, claiming the life of one person every 33 seconds. (1) 

As research unfolds, questions about the accuracy of traditional lipids tests in predicting heart disease risk continue to arise.

In response, advanced lipid testing has emerged, providing a more comprehensive look at heart disease risk.

Here, you’ll learn about advanced lipid testing – what it is, why it’s important, and how to use it in your functional nutrition practice.

 

What is advanced lipid testing?

First, let’s go over a traditional lipid panel, which measures the following:

  • Total cholesterol (TC)
  • Very low-density lipoprotein cholesterol (VLDL-C)
  • Low-density lipoprotein cholesterol (LDL-C) aka “bad” cholesterol
  • High-density lipoprotein cholesterol (HDL-C) aka “good” cholesterol
  • non-HDL-C
  • Triglycerides

A person’s heart disease risk often depends on LDL-C and HDL-C levels. While valuable, these labs alone don’t paint a complete picture. This was highlighted in a 2009 study that examined lipid levels in hospitalized patients with coronary artery disease (CAD). The study found that half of the CAD patients had LDL-C levels below the recommended 100 mg/dL target. More strikingly, 75% of heart attack patients had LDL-C levels that did not indicate cardiovascular risk. (2, 3).

This raises the question: what are we missing?

A growing body of research suggests that the size, density, and number of lipoprotein particles better predict the risk of heart disease. (4, 5, 6, 7, 8). 

This is where advanced lipid testing surpasses traditional testing. It measures the distribution and size of lipoproteins alongside other traditional metrics to provide a more comprehensive view. (9)

 

What does advanced lipid testing measure?

An advanced lipid panel measures the following:

Apo A1

Apo A-1 is the main protein attached to the surface of all high-density lipoproteins (HDL). It helps remove fat and cholesterol from arterial walls by transporting them back to the liver for excretion.

Measuring apo A-1 reflects the amount of cardioprotective lipoproteins in the blood. (10, 11)

Apo A1 Goal ≥115 mg/dL

 

Image source: Familiar HDL Deficiency. MedlinePlus. https://medlineplus.gov/genetics/condition/familial-hdl-deficiency/. Published November 1, 2012. Accessed January 20, 2024. 

 

Apo B

Apo B is crucial for binding LDL particles to the LDL receptor, allowing cells to absorb LDL and cholesterol. An excess of apo B-containing particles is a primary driver of atherosclerosis. 

Measuring the total apo B value shows the total number of potentially harmful lipoproteins in the blood. (12, 13)

Apo B Goal 40-100 mg/dL

 

Buoyant HDL2b

HDL is categorized into two types based on density: large buoyant HDL2 and small dense HDL3. These types can be further divided into five subcategories: HDL2a, HDL2b, HDL3a, HDL3b, and HDL3c. (14)

While all subtypes are beneficial, the larger buoyant HDL particles may be more anti-inflammatory and anti-atherogenic than smaller and denser ones.

Among these subfractions, buoyant HDL2b is the largest and most buoyant, which makes it the most cardioprotective. 

A higher level of HDL2b is associated with better health outcomes. (14,15,16)

Buoyant HDL2b Goal ≥1500 nmol/L

 

Dense LDL III and Dense LDL IV

Like HDL, LDL consists of several subclasses of particles with different sizes and densities, including large buoyant (lb) and small dense (sd) LDLs.

Dense LDL III and IV are considered small dense LDL (sdLDL).

Compared to large buoyant LDL (lbLDL), small dense LDL (sdLDL) is significantly smaller and stickier. As a result, they’re more likely to adhere to the arterial wall, which increases the risk of atherogenesis. (17, 18, 19, 20)

Dense LDL III Goal ≤300 nmol/L
Dense LDL IV Goal ≤100 nmol/L

 

Image source: Superko H, Garrett B. Small Dense LDL: Scientific Background, Clinical Relevance, and Recent Evidence Still a Risk Even with ‘Normal’ LDL-C Levels. Biomedicines. 2022; 10(4):829. https://doi.org/10.3390/biomedicines10040829

Fasting Insulin

Research indicates that elevated insulin levels may contribute to endothelial dysfunction, inflammation, and platelet activation, all of which increase the risk of atherosclerosis. (21, 22)

Fasting Insulin Goal 3-8 mIU/mL

 

HDL

High-density lipoproteins (HDL) are important in reverse cholesterol transport. They move cholesterol from peripheral tissues, including the arterial wall, back to the liver. In the liver, cholesterol is processed, packaged into bile, and eventually excreted.

HDL particles have antioxidant and anti-inflammatory properties, offering cardioprotective benefits. (23, 24)

HDL Goal 55-70 mg/dL

 

HDL-P

A basic HDL lab test measures HDL cholesterol (HDL-C), which only assesses the cholesterol content within HDL particles. While HDL-C is inversely related to cardiovascular risk, it may not provide a complete understanding of HDL functionality.

This is why assessing HDL particles (HDL-P) is essential. HDL-P measures the overall amount of HDL particles in the blood, not just the amount of HDL-carrying cholesterol. This is important because having a normal HDL-C level doesn’t guarantee an adequate number of HDL particles.

For example, even if HDL-C falls within the normal range, if the HDL-P is low, there’s reduced protection against cardiovascular disease, particularly when the levels of Buoyant HDL2b are also low. (25, 26)

HDL-P Goal >7000 nmol/L

 

Homocysteine

Homocysteine, an intermediate protein, can damage the endothelial lining of blood vessels and increase the risk of atherosclerosis at high levels. (27)

Homocysteine Goal 3.0 – 7.2 umol/L

 

LDL

LDL is the main carrier of cholesterol in the blood (around 67%) and plays a crucial role in delivering cholesterol to various tissues in the body.

Arterial plaque is primarily made of cholesterol, and LDL is the primary carrier of cholesterol. As a result, LDL has traditionally been referred to as “bad,” although recent research proves this inaccurate. (28, 29)

LDL Goal 0.0-120 mg/dL

 

LDL-P

Like HDL-P, LDL particles (LDL-P) can vary in size. An increased LDL-P is associated with a greater risk of heart disease. (30)

LDL-P Goal <900 nmol/L

 

Image source: Lipoprotein Particle Testing. SpectraCell Laboratories. https://www.spectracell.com/lpp. Accessed January 20, 2024.

Lp(a)

Lp(a) is particularly dangerous because it inhibits plasmin formation, an enzyme that dissolves blood clots. It can penetrate the arterial wall, oxidize, and contribute to atherosclerosis.

Lp(a) only needs to be tested once in a person’s life. Most people have some amount of Lp(a) in their body, but about 1 in 5 individuals have higher Lp(a) due to genetics. Unlike other lipids, diet and lifestyle changes don’t alter Lp(a). 

People with high levels of Lp(a) are more likely to develop early heart disease, have heart attacks, and experience strokes compared to those with lower Lp(a) levels. Pharmaceutical intervention is the only treatment option for people with high Lp(a). (31, 32, 33, 34)

Lp(a) Goal <30 mg/dL

 

Remnant Lipoprotein

Remnant lipoproteins (RLPs) come from the partial breakdown of chylomicrons and very low-density lipoprotein (VLDL). They’re small and dense particles and possess significant atherogenic properties. (35)

Remnant Lipoprotein Goal <150 nmol/L

 

Total Cholesterol

Total cholesterol measures the total amount of cholesterol in the bloodstream. The following equation calculates total cholesterol: HDL level + LDL level + 20% of triglyceride.

Total Cholesterol Goal 150-200 mg/dL

 

Triglycerides

Triglycerides are the most common form of fat in the body and play a crucial role in energy metabolism. Elevated levels of triglycerides in the blood are associated with an increased risk of cardiovascular disease. (36)

Triglycerides Goal 50-80 mg/dL

 

VLDL

Very low-density lipoproteins (VLDL) are made in the liver and are composed primarily of triglycerides. Research shows that elevated VLDL contributes to the development of atherosclerosis. (37)

VLDL Goal <85 nmol/L

 

hs-CRP

High-sensitivity C-reactive protein (hs-CRP) reflects active systemic inflammation. Research suggests that a high hs-CRP strongly predicts future cardiovascular events. (38)

hs-CRP Goal <1.0 mg/dL

 

non-HDL-C

Non-HDL cholesterol includes all cholesterol except HDL. The following equation calculates non-HDL-C: total cholesterol – HDL-C.

Non-HDL cholesterol is an important measure, particularly in individuals on statin therapy. Elevated levels of non-HDL cholesterol increase the risk of cardiovascular events, even if LDL-C is normal. (39, 40) 

non-HDL-C Goal <160 mg/dL

 

non-HDL-P

Non-HDL-P is the total number of atherogenic particles in the bloodstream. The higher the non-HDL-P, the greater the risk of atherosclerosis and a cardiovascular event. (41)

non-HDL-P Goal <1000 nmol/L

 

Conclusion

While traditional lipid panels offer value, they don’t provide a complete picture. Advanced lipid testing, on the other hand, offers broader detail into a person’s lipid profile. With this information, you can develop a targeted functional nutrition plan to reduce risk and optimize overall health.

The IFNA training program covers  advanced lipid testing and nutrient interventions for cardiovascular health in Track 2 Module 4. Sign up today to learn more!

by Tori Eaton, RDN, LDN, IFNCP

 

Biomarker  Reference Range
Total Cholesterol 150-200 mg/dL
VLDL <85 nmol/L
LDL 0.0-120 mg/dL
LDL-P <900 nmol/L
Dense LDL III ≤300 nmol/L
Dense LDL IV ≤100 nmol/L
HDL 55-70 mg/dL
HDL-P >7000 nmol/L
Buoyant HDL2b ≥1500 nmol/L
non-HDL-C <160 mg/dL
non-HDL-P <1000 nmol/L
Apo A-1 ≥115 mg/dL.
Apo B 40-100 mg/dL
Lp(a) <30 mg/dL
Remnant Lipoprotein <150 nmol/L
Triglycerides 50-80 mg/dL
Fasting Insulin 3-8 mIU/mL
Homocysteine ≤3.0 – 7.2 umol/L
hs-CRP <1.0 mg/dL

 

Labs to Consider:

Cardio IQ

NMR LipoProfile

Lipoprotein Particle Testing (LPP)

 

References:

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